The objective of this application is to purchase a new confocal microscope for the Penn State Hershey College of Medicine Core Imaging Facility. Though our core facilities are available to all investigators in the College of Medicine, this request is submitted to meet the specific needs of a group of NIH-funded major users. This new microscope will permit three types of study that cannot be accomplished with our current facility. First, because the microscope will be configured specifically for live-cell studies, we can meet the rapidly growing need for more sophisticated equipment dedicated to this experimental approach. The configuration will enable precise execution of time lapse studies, fluorescence resonance energy transmission (FRET) and fluorescent recovery after photobleaching (FRAP). Second, the microscope will also have a tandem scanner to provide both high resolution and high speed scanning options. These features will be vital for high resolution imaging experiments and will allow dynamic studies of ion flow and mitochondrial status. Third, the instrument will allow the simultaneous excitation and detection of up to five different fluorophores. The availability of this new microscope will improve the ability to perform intensive live-cell imaging projects focusing on a variety of health issues including viral infections, cance, diabetes and its complications (primarily diabetic retinopathy and muscle protein synthesis), heart disease, degenerative diseases of the central and peripheral nervous system (including Parkinson's disease, Alzheimer's disease, restless leg syndrome and eye diseases such as glaucoma). The projects will use the equipment to image rapid events in live cells or explant tissue transfected with fluorescent protein markers, or labeled with metabolic dyes, to determine changes in protein expression, trafficking and redistribution in response to pharmacological, environmental or genetic manipulations. PUBLIC HEALTH RELEVANCE: The confocal microscope requested will have broad relevance to human health because it will enable us to study rapid interactions between molecules in living cells, in real time and thus aid determination of their function in health and disease. This instrument will enhance a wide variety of public health projects being conducted at the Milton S. Hershey Medical Center, including those related to cancer, diabetes, heart disease, viral infection and neurodegenerative diseases.